Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB.
The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.
Have newly diagnosed pathologically proven glioblastoma, isocitric dehydrogenase-1/2 wild-type
Tumor with methyl guanine methyl transferase (MGMT) gene promoter unmethylated
Available paraffin embedded tumor tissue for the study
Have completed standard radiotherapy with or without temozolomide
Multifocal tumor (unless all localized in a 50-mm diameter area accessible to ultrasound field) or tumor located in the posterior fossa.
Uncontrolled epilepsy.
Received other investigational agents within 2 weeks of registration
Received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.
Single group
Balstilimab
DrugBalstilimab 450 mg IV over 30 minutes every 3 weeks
Botensilimab
DrugBotensilimab1mg/kg mg IV over 30 minutes every 6 weeks
Liposomal Doxorubicin
DrugLiposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks
Sonocloud-9 (SC-9)
DeviceDevice activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks
Unacceptable toxicity rate
Unacceptable toxicity rate in cycle 1 of \< 33%
Landmark survival analyses
Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival.
Predictive value of phospho-extracellular signal-related kinase (p-ERK) expression
Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy
Response rate
Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor
Patterns of recurrence
Patterns of recurrence by magnetic resonance imaging related to sonication field
Immune profile
Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival
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